Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial Outcomes: Proteomic Analysis of Perfusates from Livers Undergoing Normothermic Machine Liver Perfusion Reveals Biomarkers Predictive of Graft Viability and Post-Transplant Complications
1Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom, 2The School of Biosciences Proteomics Facility, University of Birmingham, Birmingham, United Kingdom, 3Liver Unit, Queen Elizabeth University Hospital, Birmingham, United Kingdom, 4Liver Unit, The Queen Elizabeth University Hospital, Birmingham, United Kingdom, 5The Liver Unit, Queen Elizabeth University Hospital, Birmingham, United Kingdom
Meeting: 2019 American Transplant Congress
Abstract number: B37
Keywords: Donors, marginal, Liver transplantation, Machine preservation, Post-operative complications
Session Information
Session Name: Poster Session B: Biomarkers, Immune Monitoring and Outcomes
Session Type: Poster Session
Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: The VITTAL clinical trial demonstrated that post-ischaemic normothermic machine perfusion(NMP) can increase utilisation of livers from the marginal pool of extended criteria donors (ECD). Here we sought potential biomarkers predictive of liver transplantability and post-transplant outcomes.
*Methods: Perfusate samples from 31 VITTAL trial perfusions were collected sequentially until the end of each perfusion run. Untargeted Liquid Chromatography/Mass Spec. proteomic analysis was then carried out.
*Results: A higher total number of liver derived target proteins were detected in the non-transplanted group(NTG) compared with the transplanted group(TG) (931 +/- SEM 74 vs 520 +/- SEM 41 respectively p >0.0005) with no significant difference between Donors after Circulatory Death vs Donors after Brain Death livers. A group of 10 target proteins were uniquely detected in 22/22 TG livers. No unique protein targets were detected in the NTG, however livers from the TG livers which went on to develop Ischaemic type biliary lesions(ITBL), early allograft dysfunction(EAD), post reperfusion syndrome(PRS)and acute kidney injury(AKI), a series of 7 proteins were uniquely detected. Of the 22 TG liver, perfusates from those that developed ITBL contained 2 unique proteins; EAD combined with NTG also contained 2 unique proteins; no protein targets were detected in PRS; Perfusates from the TG livers which developed AKI contained 19 unique detectable protein targets.
*Conclusions: Untargeted proteomics was able to identify clusters of proteins which discriminate between transplantable and non-transplantable livers. In addition it was also able to identify markers predictive of post-transplant complications. This suggests that objective point of use tests could be developed to augment the current subjective transplantability criteria. thereby increasing safety of transplantation of NMP ECD livers. It may also assist in early identification of those livers which may develop significant PT complications.
To cite this abstract in AMA style:
Afford S, Wallace L, Attard J, Boteon Y, Laing R, Yu J, Perera T, Mirza D, Mergental H. Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial Outcomes: Proteomic Analysis of Perfusates from Livers Undergoing Normothermic Machine Liver Perfusion Reveals Biomarkers Predictive of Graft Viability and Post-Transplant Complications [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/viability-testing-and-transplantation-of-marginal-donor-livers-vittal-trial-outcomes-proteomic-analysis-of-perfusates-from-livers-undergoing-normothermic-machine-liver-perfusion-reveals-biomarkers/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress